Pain
-
Diabetic neuropathy, often associated with diabetes mellitus, is a painful condition with no known effective treatment except glycemic control. Studies with neuropathic pain models report alterations in cannabinoid and opioid receptor expression levels; receptors whose activation induces analgesia. We examined whether interactions between CB1R and opioid receptors could be targeted for the treatment of diabetic neuropathy. ⋯ Because the peptide endocannabinoid, hemopressin, caused a significant potentiation of MOR activity, we examined its effect on mechanical allodynia and found that it blocked allodynia in wild-type mice and mice with diabetic neuropathy lacking DOR (but have CB1R-MOR complexes). However, hemopressin does not alter the levels of CB1R-MOR complexes in diabetic mice lacking DOR but increases the levels of CB1R-DOR complexes in diabetic mice lacking MOR. Together, these results suggest the involvement of CB1R-MOR and CB1R-DOR complexes in diabetic neuropathy and that hemopressin could be developed as a potential therapeutic for the treatment of this painful condition.
-
Chronic pain and sleep problems frequently co-occur. Pain itself disturbs sleep, but other factors may also contribute to sleep problems in pain patients. This cross-sectional study of 473 patients (69.9% female, mean age 47 years) entering tertiary pain management compared normally sleeping pain patients with those having recurring sleep problems to determine the relationship between pain and sleep. ⋯ Patients having sleep problems reported more use of sleep and pain medications than those sleeping normally. Findings about pain-related anxiety suggest physiological reactions as significant factors for increased sleep disturbances. These factors need to be addressed in the management of the comorbidity of pain and sleep problems, and research to understand mechanisms in these is sorely needed.
-
Randomized Controlled Trial
Observing treatment outcomes in other patients can elicit augmented placebo effects on pain treatment: a double-blinded randomized clinical trial with patients with chronic low back pain.
Clinical research on social observational learning (SoL) as an underlying mechanism for inducing expectancy and eliciting analgesic placebo effects is lacking. This double-blinded randomized controlled clinical trial investigated the influence of SoL on medication-augmenting placebo effects in 44 patients with chronic low back pain. Our hypothesis was that observing positive drug effects on pain and mobility in another patient could increase pain reduction and functional capacity. ⋯ After the intervention, pain decreased in both groups (F [1, 41] = 7.16, P < 0.05, d = 0.83), with no difference between groups. However, the SoLG showed a significantly larger decrease in perceived disability (F [1, 41] = 5, P < 0.05, d = 0.63). The direct observation of patient with chronic low back pain of positive treatment outcomes in the sham patient seems to have enhanced the treatment effects while indirect verbal reports of reduced pain did not.
-
Ivabradine, a hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel blocker and clinically approved bradycardic agent, has analgesic effects against neuropathic pain. Although the expression of HCN channels in the spinal dorsal horn (SDH) is augmented under inflammatory pain, spinal responses to centrally and peripherally applied ivabradine remain poorly understood. We investigated the spinal action and cellular mechanisms underlying the drug's analgesic effects against inflammatory pain using inflammatory pain model rats. ⋯ These phenomena were inhibited by forskolin, an activator of HCN channels. In conclusion, spinal responses mediated by HCN channels on primary afferent terminals are suppressed by central and peripheral administration of ivabradine; the drug also exhibits analgesic effects against inflammatory pain. In addition, ivabradine preferentially acts on C-fiber terminals of SDH neurons and induces a stronger inhibition of neuronal excitability in inflammatory pain.
-
Meta Analysis
Potential role of blood biomarkers in patients with fibromyalgia: a systematic review with meta-analysis.
Fibromyalgia (FM) is a complex chronic pain condition. Its symptoms are nonspecific, and to date, no objective test exists to confirm FM diagnosis. Potential objective measures include the circulating levels of blood biomarkers. ⋯ Nevertheless, this systematic literature review and meta-analysis could not support the notion that these blood biomarkers are specific biomarkers of FM. Our literature review, however, revealed that these same individual biomarkers may have the potential role of identifying underlying pathologies or other conditions that often coexist with FM. Future research is needed to evaluate the potential clinical value for these biomarkers while controlling for the various confounding variables.